to compare the efficacy of oral carbonyl iron...

DISSERTATION

TO COMPARE THE EFFICACY OF ORALCARBONYL IRON VERSUS FERROUS

SULPHATE IN MODERATELY ANEMICPREGNANT WOMEN BELONGING TO 24-32

WEEKSOF GESTATION

Submitted in partial fulfillment ofRequirements for

M.D. DEGREEBRANCH II – OBSTETRICS AND

GYNAECOLOGYEXAMINATION - MARCH 2010

OfTHE TAMILNADU DR.M.G.R. MEDICAL

UNIVERSITY, CHENNAI

STANLEY MEDICAL COLLEGECHENNAI – 600 001.

CERTIFICATE

This is to certify that this dissertation titled “TO COMPARE

THE EFFICACY OF ORAL CARBONLY IRON VERSUS

FERROUS SULPHATE IN MODERATELY ANEMIC

PREGNANT WOMEN BELONGING TO 24-32 WEEKS

OF GESTATION”.

Submitted by Dr. P. PRIYADARSENE appearing for Part II

M.D. Branch II Obstetrics and Gynecology Degree examination in

March 2010 is a bonafide record of work done by her under my direct

guidance and supervision in partial fulfillment of regulations of

the Tamil Nadu Dr. M.G.R. Medical University, Chennai.

I forward this to the Tamil Nadu Dr.M.G.R. Medical University,

Chennai, Tamil Nadu, India.

HEAD OF THE DEPARTMENT,Department of Obsterics and

Gynaecology,Govt. RSRM Lying-in Hospital,Govt. Stanley Medical College,

Chennai – 600 013.

DEAN,Govt. Stanley Medical College &

Hospital,Chennai-600 001.

ACKNOWLEDGEMENT

I whole-heartedly thank with gratitude Dr.A.PRIYA, M.S., D.O. Dean

Govt. Stanley Medical College and Hospital and Dr. S.CHITRA, M.D.,

PhD., the Dean of Government Stanley Medical College, Chennai for having

permitted me to carry out this study at the Government RSRM Lying-in

Hospital, Stanley Medical College.

I am greatly indebted to Prof. Dr. C.VENI, M.D.D.G.O., DipNB

Superintendent of Govt. RSRM Lying-in Hospital, Chennai for providing

with necessary facilities to carryout the study and for her continues support,

guidance and encouragement.

I will be failing in my duty if I do not make a special mention about

Prof. Dr. N.HEPZIBAH KIRUBAMANI, MD.D.G.O., Ph.D., Professor of

Obstetrics and Gynecology, Government RSRM Lying -in Hospital who

evinced keen interest and spared much of her precious time in making critical

analysis and inspiring comments which enabled me to crystallize my ideas in

the best of fashion possible. Her valuable instructions and sagacious

counseling provided me the necessary and requisite encouragement ,

motivation and impetus to complete this thesis successfully with ease and

grace.

I express my sincere thanks to Prof. Dr.A.KALAICHELVI,

M.D.D.G.O., DipNB, Prof. Dr.A.P.NALINI, M.D.D.G.O., and

Prof. Dr.T.RUCKMANI, M.D.D.G.O., Professors of Obstetrics and

Gynaecology for their guidance in carrying out this study.

I am thankful to all my Assistant Professors, Government RSRM

Lying-in Hospital for their kindness and support throughout my study.

I sincerely acknowledge the help and assistance rendered by my fellow

postgraduates. Last but not the least, my gratitude and heart felt thanks to all

the patients for extending full co-operation during the study.

CONTENTS

S.NO. TITLE PAGE NO.

1. INTRODUCTION 1

2. AIM OF THE STUDY 5

3. REVIEW OF LITERATURE 6

4. MATERIALS AND METHODS 45

5. OBSERVATIONS AND RESULTS 49

6. DISCUSSION 67

7. SUMMARY 70

8. CONCLUSION 71

9. MASTER CHART

10. PROFORMA

11. BIBLIOGRAPHY

1

INTRODUCTION

Anemia in pregnancy exists world over but is a very

common problem in most of the developing countries. Anemia is

major public health problem in economically disadvantaged

segments of population in developing countries.

In country like India it is frequently severe and contributes to

maternal morbidity and mortality. It deserves more attention than

what it is currently receiving. Recently lot of programmes have

been focused on safe motherhood but maternal anemia a

problem of great concern.

Gender discrimination also plays a major role in increasing

the prevalence of anemia in developing countries.

Magnitude of Problem

The world wide prevalence of anemia in pregnant women is

estimated at 51% WHO states that 35% to 75% of pregnant

women in developing countries and 18% of women in

industralised countries are anemic.

2

In India, the incidence of anemia among expectant mothers

is alarmingly high with hemoglobin level less than 10 gm%, 15 to

30% of maternal deaths are due to anemia.

In areas where malaria and hookworm infestation is

endemic prevalence of anemia is high as 91%. The incidence of

anemia is adolescent girls in slum areas estimated to 98% this

adversely affect reproductive performance.

The prevalence of anemia has come down due to

fortification, prophylactic iron supplementation and better health

care programmes aimed at woman and children.

NEED FOR THE STUDY

Anemia is the most important complication in pregnancy in

the developing countries not only because of its greatly increased

incidence but also because of its severity (Agarwal et al., 1999).

Several studies reveal that socioeconomic cultural factors

influence dietary inadequacy during pregnancy which is attributed

to poor purchasing power, literacy, ignorance, regarding nutritive

value of readily available cheaper food stuffs, cultural taboos,

3

superstitions and large family (Menon Krishna et al., 1995; Ruth

Bunnet and Brown Linding, 1993; Naik D. Jayashree, 1992).

Nutritional iron deficiency anemia is a serious problem in

pregnancy which affects 90% pregnant women.

Severe forms of anemia in the third trimester of pregnancy

are invariably associated with cardiac failure. Highest maternal

mortality rate in developing countries is due to severe anemia,

contributing to 20% death both, directly and indirectly. It is also

responsible for incidence of premature and low birth weight

babies thus increasing perinatal and infant mortality and

morbidity.

According to Hassan Masood (1991), anemia is prevalent

among 50% - 90% of pregnant women especially in India, which

is the number one killer. Despite considerable improvement and

awareness in the antenatal care in developing countries and

in spite of national anemia prophylaxis programme in India

anemia remains a problem of great concern with regard to

maternal morbidity, mortality and adverse outcome (Singh

Kishore et al., 1995).

4

Due to the above stated reasons this study emphasis on

regular antenatal check up, to screen for anemia during every

check up detect it earlier so that it can be treated adequately

before the mother reaches term gestation. The goal of the

treatment is to increase the hemoglobin status as rapidly as

possible.

5

AIM OF THE STUDY

To Compare

The response in each group by observing the rise in

hemoglobin which can be a good predictor for oral

iron therapy.

The side effects in both groups of drugs

The patient compliance in both groups, and then by

assessing the efficacy of ferrous sulphate and

carbonyl iron in moderately anemic pregnant women,

belonging to 24 to 32 weeks of gestational age.

6

REVIEW OF LITERATURE

Definition of Anemia

Anemia is a condition of low circulating hemoglobin (Hb) in

which the Hb concentration has fallen below a threshold lying at

two standard deviations all below the median of healthy

population of the same age, sex and stage of pregnancy.

WHO definition for diagnosis of anemia in pregnancy is a

Hb concentration of less than 11 gm / dl and a hematocrit of less

than 33%, although CDC (Centers for Disease control USA)

proposes a cutoff point of 10.5 gm/dl during the second trimester.

Severity of Anemia

The Indian Council of Medical research uses four

categories of anemia depending upon the hemoglobin levels in

their study are:

7

S. NO Category Hb Status gm/dl

1. Mild 10-10.9

2. Moderate 7-10

3. Severe

8

c. Hemolytic

Familial Hemoglobinopathies

Acquired Malaria, Severe Infection

d. Bone Marrow Insufficiency

Hypoplasia or aplasia due to radiation, drugs

(aspirin, indomethacin)

CAUSES OF NUTRITIONAL ANEMIA DURING PREGNANCY

Nutritional Anemia is believed to be the most widespread

nutritional disorders in the world. It essentially affects people in

developing countries According to WHO 500 million to I billion

individuals representing 15 to 20 percent of world’s population is

presently affected by this condition.

According to WHO definition, the “nutritional Anemia”

encompasses all pathological conditions in which the blood

hemoglobin concentration drops to an abnormally low level owing

to a deficiency in one or several essential nutrients, regardless of

the cause of this deficiency.

9

The etiology of nutritional deficiency of iron in developing

countries is multifactorial. The causes include nutritional

deficiency of iron, folate and vitamin B12. Secondary effects of

infections and parasitic infestation. An imbalance occur as a

result of low nutrient intake, poor absorption, increased demand

of nutrients during pregnancy, increased nutrient loss due to

repeated pregnancies, short birth interval and menstruation.

Dietary short coming are often associated with low socio

economic status and related to cooking and dietary habits, local

food taboos, ignorance, illiteracy and lack of knowledge regarding

nutrition (Van De, 1998).

The etiological factors of nutritional Anemia in pregnancy

a. Dietary factors.

b. Increased demand during pregnancy

c. Maternal causes

d. Sociocultural factors

e. Infections and infestation.

10

a) Dietary factors

Inadequate intake of food

a) Low nutrient intake is the commonest cause of

nutritional anemia.

b) Main nutrients involved in synthesis of hemoglobin are

iron, folic acid, Vit B12 and deficiency of these cause

anemia.

Low iron absorption

Poor absorption and utilization of iron in the body is one of

the causes of iron deficiency anemia during pregnancy.

Factors decrease Iron absorption

a) Phytates

b) Calcium

c) Tannins

d) Tea and coffee

e) Herbal drinks

f) Fortified iron supplements.

11

b) Increased Demand during pregnancy

Increased Demand for nutrients is one of the major of

nutritional anemia during pregnancy (Bucksher et at., 1996). The

increased blood volume during pregnancy results in dilution of red

cells and a reduction in hemoglobin concentration. This dilutional

anemia is potentially accentuated by the increased demands of

iron folic acid leading to anemia.

Poor absorption of iron occurs due to the fact that Indian

Diet is predominantly cereal based.

Though Indian diet has adequate iron content 20–25

mg/day several factors inhibits absorption, the most important

being the phytate from the cereals. Deficiency of ascorbic acid

and calcium inhibits iron absorption.

Factor Affecting Absorption

Factors increase absorption

a) Hydrochloric acid by favoring dissolution and

reduction of ferric iron.

12

b) Reducing substance like ascorbic acid, amino acids

containing sulphydryl radical, these reduce ferric to

ferrous iron.

c) Meat contain organic iron and increased HCL

secretion.

d) Food containing low phosphorus diet.

There is increased demand for iron as it is essential for the

synthesis of increased hemoglobin required for the greater

maternal blood as well as for the storage of iron in the fetus.

When the mother does not meet this demand, she may develop

features of iron deficiency anemia. It is need not only to

compensate the usual losses in urine, faeces, cutaneous

desquamation (around 0.5 – 1 mg per day) but also to cover the

various pregnancy related expenditure. Total 1000 mg of iron is

required. This represents an extremely large amount to meet. If

not looked after it can result in iron deficiency anemia

(Hercubury, 1991).

13

The Requirements of iron is not confined only to those

aspects of the fetus but also the placenta, the enlarged uterus

and for increased volume that occurs during pregnancy.

The estimates of iron requirements are

Foetus : 400 mg

Placenta : 100 mg

Uterus : 50 mg

Hb : 320 mg

Total : 870 mg

c) Maternal Causes

Depletion of nutrients occur in maternal body due to various

reasons. The women may have entered pregnancy with

compromised or absent iron stores. When further iron depletion

occurs with advancing gestation anemia results (Zuspan and

Huiligun, 1994).

In tropics frequent pregnancies are the common cause of

iron and folic acid deficiency anemia among pregnant mother

(Buckshae et al., 1999) from depletion occurs due to

14

uncompensated menstrual loses and chronic blood loss due to

repeated pregnancies.

Grand multipara is considered as one of the cause

contributing to nutritional anemia during pregnancy as it is

associated with increased incidence of disorders like

hypertension, antepartum hemorrhage and others. The co-

existing pathological condition like APH, PPH, abortions lead to

iron deficiency results in iron deficiency anemia (Buckshae et al.,

1996; Modak et al., 1996).

There are maternal causes which lead to nutritional anemia

during pregnancy. These are:

a) Anemia in multigravida or multipara is mainly due to

blood loss in previous deliveries or pregnancies.

b) Repeated abortions, APH, PPH.

c) Extra demand for iron, folic acid in multiple

pregnancy.

d) Short interval between pregnancies.

15

i. Less storage of iron in the mothers body since it

is already utilized in previous pregnancies.

ii. There is no time for storage of iron in the body

for the next pregnancy.

d) Socio Cultural Factors

i) Poor socioeconomic Status.

As the women continue to be a socially disadvantaged

group their poor status affects nutrition.

ii) Cultural belief, Cooking and Eating habits food taboos.

Cultural practices play an important role in cause of

nutritional anemia in pregnancy. Because of taboos the

pregnant mothers, avoid meat, fish, egg, jaggery,

curds, milk and leafy vegetables. Over cooking of food,

washing of vegetables several time may lead to loss of

nutrients in the food. This may also lead to nutritional

anemia in pregnancy (Vande 1998).

16

e) Infection and infestation

i) Hookworm infestation

Hookworm infestation is considered as one of the

cause of nutritional anemia among the pregnant

women (Agarwal et al., 1999).

Infestation with hookworm, roundworm and whipworm

cause or aggravate iron deficiency anemia

(Sephension, 1994).

Hookworm infestation also leads to the deficiency of

folic acid in pregnant women (Buckshae et al.,

1996).

ii) Malaria

Plasmodium falciparam cause profound anemia

during an acute infection among pregnant woman

(Agarwal et al., 1999).

Erythropolesis

In human embryo hemopoiesis is first evident in yolk sac at

2 months, liver at 3rd month and to some extent spleen between

17

3rd and 6th month. Bone marrow activity begins by 4th and 6th

month, it completely take over the process of hemopoiesis.

At birth bones are filled with red marrow, by 7 years marrow

in long bones is less active, by age of 10 to 14 years fatty marrow

extends proximally and 18 years normal adult distribution of

marrow is in the skull, axial skeleton, pelvis shoulder, sternum

ribs and with extension of proximal ends of long bones.

Stages of Erythropoiesis

i) Basophyllic proerythroblast

ii) Early Normoblast

iii) Intermediate normoblast

iv) Late normoblast

v) Reticulocyte

vi) Erythrocyte

Kinetics of Erythropoiesis

The time taken for erythropoiesis in human beings is about

7 days. The first 5 Days are occupied by division and maturation

upto non nucleated reticulocytes in the marrow and the

18

reticulocytes normally mature for another 24 hours in the

peripheral blood and spleen, after which it circulate for 120 days.

Since about 1% circulating erythrocytes are destroyed each day,

same number are formed and released. Factors regulating

erythropoiesis.

a) Androgen stimulates, esterogen suppresses

erythropoiesis,

b) Thyroid hormone and adrenocortical steroids

stimulates erythropotesis

c) Nutritional factors like proteins. Vit B12 folic acid , Vit

B6, riboflavin. Pantothenic acid, nicotinic acid, ascorbic

acid, Vit E, mineral like copper cobalt, zinc and iron.

IRON COMPARTMENTS IN HUMAN

Hemoglobin: 1ml of packed RBC contain 1mg of iron and

size of this compartment changes in anemia.

Storage: Ferritin and haemosiderin.

19

Ferritin: It is a water insoluble complex of ferric

hydroxide and protein apoferritin. Uptake and release of iron by

ferritin is very rapid. Ferritin occurs in all cells of the body. Its

concentration correlates with iron store. Hemosiderin water

soluble compound found predominantly in cells of monocytes

macrophage system.

Myoglobin: Present in all skeletal and cardiac muscles

cells.

Transport Iron: Active transport process explained by

“Mucosal Block Theory”. According to this theory ferrous form

absorbed in small intestine converted to Ferric form in the

intestinal villi combine with apoferritin in the villous epithelial cell

to form ferritin. Absorption of iron is controlled by the availability

of apoferritin. If this is fully saturated no more iron is absorbed,

and this protects from excessive absorption in anemia. In anemia

excess ferritin is broken down to make more apoferritin available

and thereby augments iron absorption. This intracellular ferritin is

eventually excreted following desquamation of epithelial cells of

intestine.

20

IRON TRANSPORT AND UTILIZATION

Iron after absorption circulate in the blood bounded to a

globulin transferrin which is normally 1/3 saturated with iron.

Normal iron varies from 66 -140 microgram / 100 mg plasma.

Physiological changes in Hemoglobin during pregnancy

In pregnancy there is progressive increase in circulating

blood volume due to increase in plasma and RBC volume.

Increase blood volume ranges from 30 – 70% of the non

pregnant level.

Increase blood volume due to maternal size, level of

placental and extra placental hormones and erythropoietin,

influence the increase in blood volume.

The increase in plasma volume is 40 – 50%

The increase in RBC volume is 20%.

Anemia during pregnancy is a consequence of primarily of

expansion of plasma volume without normal expansion of

maternal hemoglobin.

21

This is called physiological anemia because

i) It begins in second trimester when the iron needs are

fully met.

ii) Occurs in well nourished women

Physiological Anemia Occurs Because

i) Increase in plasma volume and RBC volume occur at

different periods of pregnancy.

ii) Plasma volume begins to rise at 6 -8 weeks of

pregnancy reaches peaks at about 32 weeks after it

plateaus.

iii) The rise in RBC volume begins at 20 weeks and

continue till term. There is trend for mean Hb fall in

the first and second trimester and little rise later in the

third trimester (Peck and Ariyes, 1979.)

Hematological parameters

Normal blood values in non pregnant status.

RBC - 4.8 - 6 million / cumm

Hb - 12 – 14 gm / dl

PCV - 40 – 45%

22

Life span of RBC is 110 -120 days.

Normal blood values during pregnancy

RBC - 4.5 million / cumm

PCV - 37 – 42%

MCV - 80 – 90 cubic microns

MCHC - 28 – 34%

MCH - 27 – 32 picogram

Colour Index - 0.9 – 1

Hb in gm per 1000ml bloodMean corpuscular Hb MCH =

RBC in million / cumm

Normal = 27 - 32 Picogram

Volumes of packed cell per 1000mlMean corpuscular Hb MCV =

RBC in million / cumm

Normal = 80-90 cubic microns

23

Mean corpuscular Hb = Hb in gm per 100 ml

Concentration MCHC___________________________ × 100 Volumes of packed cell per 100ml

Normal = 34 percent

Hb (percentage of normal)Colour Index = _______________________

RBC (percentage of normal)

Normal = 0.9 – 1

Symptoms and signs

Symptoms: complaints of fatigue, poor tolerance of

exertion, weakness and lassitude. Other features are anorexia

and indigestion, palpitation caused by ectopic beats, dyspnoea,

giddiness and swelling of legs.

Signs

Pallor

Pallor of varying degree is evident. The colour of the lips,

tongue, inner side of the lower eyelid, palms, and sole are pale. If

24

the colour of palmar creases are as pale as the surrounding skin

the hemoglobin is usually less than 7 gm/dl.

Nailbed should be examined for pallor, the rapidity of

capillary refill is an indicator of integrity of the cardiovascular

system.

Koilonychia

Koilonychia is strongly suggestive of Iron deficiency and is

demonstrated as spoon shaped nails.

Glossitis

Ulceration in the mouth and tongue. The painful dry tongue

of glossitis is helpful in diagnosing Vit B12 deficiency anemia.

Angular stomatitis is also associated.

Oedema legs

This is due to hypoproteinemia.

25

Cardiovascular Changes

Cardiovascular signs reflect decompensation, a soft systolic

murmur may be heard in mitral area due to mitral incompetence.

Crepitations may be heard at the base of lungs due to

congestion.

Investigation

1. Maternal condition.

2. Fetal Condition.

Maternal condition: a)Type and degree of severity.

The investigations include,

a) Hb%

b) RBC Count.

c) Blood indices.

MCV – Normal 78 -92 cu micron.

92 macrocytic follate def.

26

MCH – Normal 28 -33 pgm.

In iron deficiency anemia

MCHC – 33 – 36 %

In iron deficiency anemia

Peripheral smear

MICROCYTIC HYPOCHROMIC BLOOD PICTURE

This is simple investigation often throws light on the etiology

a) Microcytic hypochromic cells.

b) Macrocytic hyperchromic cells.

c) Normocytic normochromic cells.

27

1) Microcytic hypochromic calls are seen in

a) Iron deficiency.

b) Thalessemia.

c) Sideroblastic anemia.

d) Anemia of chronic disease.

e) Lead poisoning.

f) Copper poisoning.

2) Macrocytic hyperchromic cells.

a) Follate/ vit B12 deficiency.

3) Normocytic normochromic.

a) Other causes or early nutritional deficiency

4) Schisto / aniso and poikilocytes:

Hemolytic anemia.

5) Target cells:

Thelessemia.

6) Sickle cells.

Sickle cell anemia.

28

7) Hypersegmented polymorphs.

Seen in megaloblastic anemia.

8) Platelet:

May be decreased.

9) Parasites:

Such as malaria and leishmania may be seen.

B) INVESTIGATION FOR ETIOLOGY

Urine examination :

Urine albumin, sugar and deposits, and urine culture and

sensitivity to rule out infection.

Stool examination :

- Parasites (ova of hookworm)

- Occult blood loss.

29

C) SPECIAL INVESTIGATIONS

1. Ferrokinetics:

These are tests that confirm the diagnosis and

severity of iron deficiency anemia.

a) Serum ferritin

Normal - 15-300 g/l

Abnormal when

30

e) RBC protoporphyrin – 30 gm/dl. This value is

found doubled or tribled.

f) Total iron binding capacity

Normal 350 – 400 g / 100 ml

Increased in iron deficiency anemia.

g) Free erythrocyte protoporphyrn (FEP): substrate

used for heam synthesis

Increased in iron deficiency anemia

Mild IDA - zinc protoporphyrin concentration

between 40–70 µ mol/ml

More advance IDA – ZPP is > 70 µ mol/ml

h) Serum Transferrin receptor measured by ELISA

This is new method to assess cellular iron

status. It is particularly valuable in identifying

iron deficiency anemia in pregnancy, since it is

the only measurement to accurately reflect the

iron deficit between the point of storage iron

depletion and development of anemia.

31

2. Investigations in magaloblastic anemia.

a) MCV 110 – 140 cubic microns.

b) MCH 33 – 36 picograms.

c) Serum follate

32

5. Screening test

Hemoglobin must be determined by Sahils

hemoglobin method at the first antenatal visit. It

should be repeated in all antenatal visit ideally at 32

weeks gestation when their haemodilution is at its

peak.

Effects of nutritional anemia during pregnancy

Nutritional anemia among pregnant women is associated

with adverse consequences to both the mother and the foetus.

These adverse effects vary upon the severity of anemia and

presence of other obstetric or systemic problems in anemic

women (Lewis and Chamberlin 1999).

Effects on the mother

1) Iron deficiency anemia among pregnant women leads

to diminished work capacity, physical performance

and neurological dysfunction.

2) More prone for infections.

33

3) Antepartum and postpartum haemorrhage are more

common in anemic mothers.

4) Antenatal mothers go for cardiac failure during labour.

5) Puerperal pyrexia.

6) Puerperal sepsis.

7) Subinvolution of uterus.

8) Lactational failure

9) Episiotomy wound gaping and abdominal wound

gaping.

10) Abortion.

11) Folate deficiency leads to PIH, abruptioplacenta

12) Maternal and perinatal morbidity and mortality

increased in anemic mother

Effect on fetus

Nutritional anemia due to iron and folic acid deficiency is the

cause of abortion, premature birth, low birth weight, foetal

wastage like abortion, intrauterine death, and stillbirth occur in

34

about 20% of the conception due to anemia (Sethi et al., 1991;

Kelton et al., 1988) IUGR, impaired learning ability in children.

Folic acid deficiency has been implicated as a cause

of foetal malformation especially neural tube defects.

Maternal iron deficiency anemia leads to lower iron

rescue in infancy.

Severe nutritional anemia among pregnant mother

leads to increased risk of intrauterine hypoxia, higher

perinatal and neonatal mortality and morbidity.

PREVENTION OF IRON DEFICIENCY ANEMIA

Prophylaxis of non pregnant women

Girls in India are deprived of good diet. As most women

start their pregnancy with anemia or low iron stores, prevention

should start even before pregnancy. The women of childbearing

age should receive 60mg of iron daily for 2 – 4 months along with

folic acid to prevent neural tube defects.

35

Iron supplementation during pregnancy

The ministry of health government of India now

recommended intake of 100mg of elemental iron 500 µgm folic

acid in the second half of pregnancy for a period of at least 100

days.

Treatment of hookworm infestation

Single dose albendazole 400mg or mebendazole 100 mg

twice daily for 3 days with iron supplementation should be given

to all anemic pregnant women.

4. Improvement of dietary habits

Pregnant woman should eat foods rich in iron jaggery,

green leafy vegetables like spinach, mustard leaves, turnip green,

cereals, sprouted pulses. Avoid tea and coffee intake, too much

cooking should be avoided.

5. Proper antenatal care

a) Antenatal mothers should have regular antenatal

checkup which should begin in first trimester of

pregnancy.

36

b) Hb% estimation should be done during every A.N.

visit.

c) Iron and folic acid should be consumed daily.

d) Proper treatment of infection.

6. Health education

1. By limiting number of children 1 to 2.

2. The ideal interval between 2 successive pregnancy

should be 3 year.

3. Ideal age for child bearing is 20 – 25 yrs.

TREATMENT OF IRON DEFICIENCY ANEMIA

Oral iron therapy

If the women presents in mid trimester or early third

trimester with anemia oral iron is started. Plenty of iron

preparation are available each with own advantages and

disadvantages.

37

Dosage

Ferrous sulphate tablets are used in all government hospital

for oral treatment of anemia. For treatment more than 180 mg of

elemental iron per day is required. Two tablets of ferrous sulphate

each containing 100 mg of elemental iron per day is required for

treatment.

Side effects

Upto 10% of women may have side effects with oral iron in

the form of gastrointestinal symptoms such as nausea, vomiting,

constipation, abdominal cramps and diarrhea, which are dose

related, side effects can be minimized by advising to take the

tablet with food.

Response to treatment

The patient’s response to 180 mg elemental iron per day is

fast with significant increase in Hb from 0.3 to 1 gm per week.

Reticulocytosis occur within 5 – 10 days of treatment.

38

Duration of treatment

Treatment should be continued until the blood parameter

become normal after which a maintenance dose of 1 tablet per

day should be continued for at least 3 months after delivery.

Disadvantage of oral treatment

a) Intolerance of medication.

b) Noncompliance.

c) Unpredictable absorption.

d) Hemoglobin concentration restored with therapeutic

dose but replenishing iron stores required treatment

for longer periods.

If there is no significant clinical or hematological

improvement within 8 weeks diagnostic reevaluation is needed.

Reasons for failure to oral therapy involve inaccurate diagnosis of

other causes of microcytic anemia such as thalessemia,

phyridoxine deficiency, lead poisoning, continuous loss of blood

through hookworm infestation, co-existing infection, faulty iron

absorption concominant folate deficiency.

39

Carbonyl iron Conventional iron

a) Ferrous sulphate

Ferrous sulphate available in government hospital contains

100 mg of elemental iron.

b) Carbonyl iron

The name Carbonyl iron comes from its process of

manufacturing. This is a pure form of elemental iron that contains

98% mineral iron which is a small particle preparation of highly

purified metallic iron. It is a form of elemental iron produced by a

chemical carbonyl decomposition process. Carbonyl describes

the process of manufacture of iron particles from iron penta

carbonyl gas.

40

Features

Carbonyl iron is the purest form of iron; it is inert and hence

cannot be chelated.

Bioavailability

Carbonyl particles are small < 5µ and have large surface

areas which results in improved bioavailability.

Carbonyl iron has been shown to be well absorbed and

utilized in Hb synthesis. Its advantage includes environmental

stability.

Safety Profile

Carbonyl iron is much less toxic than ionized forms of iron.

In humans lethal dose of ferrous sulphate is 200 mg/kg. In recent

study no serious toxicity was reported in all patients with mean

carbonyl iron ingestion of 11.2 gm/kg.

41

Side effects

Carbonyl iron does not have many of the side effects

associated with other iron product particularly ferrous sulphate

such as GI irritation, nausea, constipation or diarrhea. There was

no evidence of hematologic, hepatic or renal toxicity.

Advantages of carbonyl iron

i) It is 98% pure form. The percentage of elemental iron

in carbonyl iron is 100%.

ii) Unlike other preparation it is inert and incapable of

reacting with chelators of iron such as transferrin and

desferraxamine.

iii) It leads to rapid rise in hemoglobin.

iv) It is a wide margin of safety.

v) It is free from gastric side effect.

vi) It is safest in pregnancy.

42

MANAGEMENT OF LABOUR IN ANEMIC PATIENTS

First Stage

Patient should be in a comfortable position. Sedation and

pain relief should be given. Oxygen should he kept ready and is

given if dyspnoea. In case of preterm labour, betamimitics and

steroids should be given with caution to avoid risk of pulmonary

oedema. Digitalization may be required in cardiac failure due to

anemia. The aim is to deliver vaginally.

Second Stage

The second stage is very stressful as the patients may go in

for cardiac failure. Prolongation of second stage can be curtailed

by forceps.

Third Stage

Third stage must be energetically treated as these patients

tolerate bleeding very poorly. Prophylactic methergin should be

given. Oxytocin 20 U infusion slowly given. Episiotomy wound

should be sutured faster.

43

Puerperium

During puerperium mother should have adequate rest. Iron

and folate therapy should be continued for at least 3 months. Any

infection must be energetically treated. The anemic patient

must use an effective method of contraception and should not

conceive for at least 2 years until the iron stores are replenished.

Sterilisation is preferred if the family is completed.

Several studies were done to compare the efficacy of

different treatment using oral and parentral iron.

A prospective partially randomized study of pregnancy

outcomes and hematologic responses to oral carbonyl iron

treatment in moderately anemic pregnant women This was done

in Moulana Azed Medical Collage, New Delhi, conducted by Jaib

Sharma, Sandya Jain, Venkatesan Malika, Tejinder Singh, Ashok

Kumar, This study compared the safety and efficacy in treating

pregnancy anemia with carbonyl iron and ferrous sulphate.

Changes in haemoglobin iron indicators, pregnancy outcomes

and birth weight were compared between the 2 groups. The result

obtained were serum ferritin concentration rise after carbonyl iron

treatment better than oral ferrous sulphate group.

44

Similar other studies

1. “A novel regime carbonyl iron therapy” Srivastava

Aarthi, Tanden Prabha, Darvineta conducted in ICMR

Deparment of Obstetric and Gynaecology KGMU

Lucknow.

2. carbonyl iron the treatment of iron deficiency anemia

of pregnancy stein ML. Gunston KD, Mey RM.

3. New Schedule of carbonyl iron administration for

pregnant women Mahale AR. Shah SH.

Bioavailability of carbonyl iron a randomized double blind

study Devasthali SD. Gordeuk VR. Brittenham GM. Bravo JR,

Compared ferrous sulphate with carbonyl iron in blood donors.

The Study Showed bio availability of carbonyl iron was better with

carbonyl iron.

High does carbonyl iron in iron deficiency anemia a

randomized double blind trial Gordeuk, Britterbharm. The study

concluded that high dose carbonyl iron was well tolerated than

standard ferrous sulphate in higher dosage.

45

MATERIALS AND METHODS

The study was conducted from April 2009 – September

2009 at Government RSRM Lying – Hospital attached to Stanely

Medical College, Chennai.

The antenatal women attending the antenatal OPD between

the gestational age of 24 – 32 weeks were screened for Hb status

and 200 antenatal women who were having Hb between

8 – 9.5 gm% were selected for the study.

Exclusion Criteria

1. Gastrointestinal bleeding or mal-absorption, Bleeding

piles and bleeding from any other site is excluded.

2. Previous blood transfusion

3. Recent administration of iron for treatment of anemia

4. Woman with parasitic infection

5. Multiple pregnancy

46

6. Woman with diabetes, hypertension significant

medical complication such as heart disease or any

other systematic disease are excluded.

INCLUSION CRITERIA

Gestational age 24 – 32 weeks of pregnancy

Moderately anemic (Hb 8 to 9.5 gms %) pregnant

woman attending OPD at RSRM

INVESTIGATION PERFORMED

1. Hb estimation by Sahlis hemoglobinometer

2. Peripheral smear with Leishman Stain

3. Packed cell volume

4. Mean corpuscular volume

5. Mean corpuscular hemoglobin concentration

6. Motion ova and cyst

7. Bleeding time

8. Clotting time

47

METHODOLOGY

In all pregnant woman included in the study a written

informed consent was obtained.

Both the groups were allocated in such a way that body

mass index, gestational age and hemoglobin status initially was

equal in both treatment groups.

After selection patient was subjected to detailed history &

physical examination.

All patient subjected to investigation like hemoglobin,

peripheral smear, packed cell volume, mean corpuscular volume,

mean corpuscular hemoglobin concentration, platelet count,

bleeding time, clotting time and motion ova cyst.

THE TWO TREATMENT GROUPS ARE

100 of selected Group A received ferrous sulphate one

tablet of 100 mg of elemental iron thrice a day with folic acid

0.5 mg one tablet per day.

48

100 of selected Group B received carbonyl iron one tablet

of 100 mg of elemental iron twice a day with folic acid 0.5 mg one

tablet per day.

Patient evaluated apart from baseline at 2 weeks interval.

Clinical evaluation for anemic improvement like improvement in

appetite and well being was enquired. Patient was also enquired

about the drug complications like gastritis and about the colour of

the stool. Adverse effect if any reported, were noted and vital like

blood pressure and pulse rate were noted. Patient should be

bring back the used empty pack.

At the end of 4 weeks, repeat hemoglobin and hemotocrit

estimation was done. The results and data was analyzed with

statistical test.

49

OBSERVATION AND RESULTS

Table 1

Group A FerrousSulphate

Group B Carbonyl IronInitial Hb

gm % No. ofPatients

PercentageNo. of

PatientsPercentage

8 to 8.5 23 23% 25 25%

8.5 to 9 28 28% 28 28%

9 to 9.5 49 49% 47 47%

In this study in Group A ferrous sulphate 23% of patient had

initial Hb 8 - 8.5 gm%, 28% had 8.5 - 9 gm% and 49% had

9-9.5gm%.

In Group B carbonyl iron 25% of patient had initial Hb of

8-8.5 gm%, 28% had 8.5-9 gm% and 47% had 9-9.5 gm%.

50

Table 2


Group B Carbonyl IronRise in Hb

gm % No. ofPatients

PercentageNo. of

PatientsPercentage

0.5 to 1 12 12% -

1 to 1.5 66 66% 34 34%

1.5 – 2 22 22% 54 54%

> 2 - 12 12%

The rise in Hb in ferrous sulphate group is 12% between

0.5 - 1 gm%, 66% had rise of 1 - 1.5 gm% and 22% had rise of

1.5 - 2 gm%.

In Group B carbonyl iron 34% of patient had rise of

1 - 1.5 gm%, 54% of patient had rise of 1.5 - 2 gm% and 12%

showed a rise of > 2 gm%.

Conclusion

P value of less than 0.001 indicates the difference in “Rise

in Hb” between ferrous sulphate group and carbonyl iron group is

highly significant (Significant at 1%).

51

INITIAL Hb gm %

25%23%28%28%

47%49%

0

10

20

30

40

50

60

Group A Ferrous Sulphate No. of Patient Group B Carbonyl Iron No. of Patient

Initial Hb gm %

No.

of a

nten

atal

mot

hers

8 to 8.58.5 to 99 to 9.5

RISE IN Hb gm %

00

22%

66%

12% 12%

54%

34%

0

10

20

30

40

50

60

70

0.5 to 1 1 to 1.5 1.5 – 2 > 2

Rise in Hb gm %

No.

of a

nten

atal

mot

hers

Group A Ferrous Sulphate No. of Patient Group B Carbonyl Iron No. of Patient

52

Table 3


Group B Carbonyl IronInitialHematocrit

in % No. ofPatients

PercentageNo. of

PatientsPercentage

23 to 26 23 23% 25 25%

26 to 29 77 77% 75 75%

In this study 23% of patient had initial Hct of 23 - 26% and

77% of patient had Hct of 26 - 29% in ferrous sulphate group.

In carbonyl iron group 25% of patient had initial Hct of

23 - 26% and 75% of patient had 26 - 29%.

INITIAL HEMATOCRIT IN %

23% 25%

77% 75%

0

10

20

30

40

50

60

70

80

90

Group A Ferrous Sulphate No. ofPatients

Group B Carbonyl Iron No. ofPatients

Hematocrit in %

No.

of a

nten

atal

mot

hers

23 to 2626 to 29

53

Table 4


Group B Carbonyl IronRise inHematocrit

in % No. ofPatients

PercentageNo. of

PatientsPercentage

1% to 4% 47 47% 12 12%

4% to 7% 53 53% 88 88%

In this study 47% of patient had rise in Hct of 1 - 4% and

53% of patient had rise of 4 - 7% of Hct in ferrous sulphate group.

In carbonyl iron group 12% had rise of 1 - 4% Hct and 88%

had rise of 4 - 7% of Hct.

RISE IN HEMATOCRIT IN %

47%

12%

53%

88%

0102030405060708090

100

Group A Ferrous Sulphate No. ofPatients

Group B Carbonyl Iron No. of Patients

Rise in Hematocrit

No.

of a

nten

atal

mot

hers

1% to 4%4% to 7%

54

Table 5

RISE IN Hb gm % IN PATIENT WITH INITIAL Hb 8 TO 8.5 gm%

Hb Rise in gm%

Group A – FerrousSulphate

Group B – CarbonylIron

0.5 to 1 6% 0

1 to 1.5 15% 12%

1.5 to 2 2% 11%

> 2 0 2%

This table shows in ferrous sulphate group 15% had a rise

of 1 - 1.5 gm%, 2% of the patient had rise of 1.5 - 2gm% and

none had rise of > 2 gm%.

In carbonyl group 12% had rise of 1 - 1.5 gm%, 11% had

rise of 1.5 - 2 gm% and 2% had rise of > 2 gm%.

55

Table 6

RISE IN Hb gm % IN PATIENT WITH INITIAL Hb 8.5 TO 9 gm%

Hb Rise in gm %Group A – Ferrous

SulphateGroup B – Carbonyl

Iron

0.5 to 1 3% 0

1 to 1.5 23% 10%

1.5 to 2 2% 17%

> 2 0 1%

In this table in ferrous sulphate group 23% of patient had

rise of Hb 1 - 1.5 gm% and 17% of patient in carbonyl iron had

rise of 1.5 - 2 gm% and 1% of the carbonyl group had rise of

> 2 gm%.

56

Table 7

RISE IN Hb gm % IN PATIENT WITH INITIAL Hb 9 TO 9.5 gm %

Hb Rise in gm%

Group A – FerrousSulphate

Group B – CarbonylIron

0.5 to 1 3% 0

1 to 1.5 28% 12%

1.5 to 2 18% 26%

> 2 0 9%

In ferrous sulphate group 28% had rise of Hb 1 - 1.5 gm%,

18% had rise of 1.5 – 2 gm% and none had rise of > 2 gm%.

In carbonyl iron group 12% had rise of 1 – 1.5 gm%, 26% of

patient had rise of 1.5 - 2 gm% and 9% of patient had rise of

> 2 gm%.

57

RISE IN Hb % FROM INITIAL Hb LEVEL BETWEEN GROUP A AND GROUP B

0 00 0

6%

3% 3%

0

15%

12%

23%

10%

28%

12%

2%

11%

2%

17%18%

26%

2%0

1%

9%

0

5

10

15

20

25

30

RISE IN Hb gm% IN PATIENTWITH INITIALHb 8 TO 8.5

gm %

RISE IN Hb gm% IN PATIENTWITH INITIALHb 8.5 TO 9

gm %

RISE IN Hb gm% IN PATIENTWITH INITIALHb 9 TO 9.5

gm %

Rise of Hb gm %

No.

of a

nten

atal

mot

hers

0.5 to 11 to 1.51.5 to 2> 2

A

B

A

B

A

B

58

Table 8

GROUP A - FerrousSulphate

GROUP B - CarbonylIronAdverse

effect No. ofPatients

PercentageNo. of

PatientsPercentage

Constipation 7 7% 4 4%

Diarrhea 3 3% 2 2%

EpigastricPain

16 16% 8 8%

Metallictaste

8 8% 12 12%

Nil 62 62% 72 72%

Vomiting 4 4% 2 2%

The adverse effect in group A ferrous sulphate as follows:

16% had epigastric pain, 8% had metallic taste, 7% had

constipation, 3% had diarrhea and 4% had vomiting and 62% had

no side effects.

In Group B carbonyl iron 12% had metallic taste, 8% had

epigastric pain, 4% had constipation, 2% had vomiting and

diarrhea and 72% had no adverse effects.

59

Table 9

GROUP A - FerrousSulphate

GROUP B - CarbonylIronPeripheral

Smear No. ofPatients

PercentageNo. of

PatientsPercentage

MicrocyticHypochromic

65 65% 58 58%

NormocyticHypochromic

18 18% 26 26%

NormocyticNormochromic

17 17% 16 16%

65% of ferrous sulphate group and 58% of carbonyl iron

group had microcytic hypochromic anemia blood picture.

18% of ferrous sulphate and 26% of carbonyl iron had

normocytic hypochromic blood picture.

17% of ferrous sulphate and 16% of carbonyl iron had

normocytic normochromic blood picture.

60

Adverse effect

3%

16%8%

62%

4%4% 2%8% 12%

72%

2%7%0%

10%20%30%40%50%60%70%80%

Constipation Diarrhea EpigestricPain

Metallicteste

Nil Vomiting

Ferrous Sulphate Carbonyl Iron

No

of

an

ten

ata

l m

oth

ers

Adverse effect

Peripheral Smear

18% 17%

58%

26%

16%

65%

0%

10%

20%

30%

40%

50%

60%

70%

MicrocyticHypochromic

NormocyticHypochromic

NormocyticNormochromic

Ferrous Sulphate Carbonyl Iron

61

Bivariate Analysis

Comparison of Age between Ferrous Sulphate Group and Carbonyl

Iron Group

Group Statistics

25.1500 4.4865124.5600 4.57114

GROUPFerrous SulphateCarbonyl Iron

AGEMean Std. Deviation

Independent Samples Test

.921 198 .358 .5900 -.67308 1.85308AGEt df P-value

MeanDifference Lower Upper

95% ConfidenceInterval of the

Difference

t-test for Equality of Means

Conclusion: P-value of 0.358 indicates the difference in Age

between Ferrous Sulphate Group and Carbonyl Iron Group is not

significant.

62

Comparison of Parity between Ferrous Sulphate Group and

Carbonyl Iron Group

PARITY_ * GROUP Crosstabulation

34 27 6155.7% 44.3% 100.0%34.0% 27.0% 30.5%

36 38 7448.6% 51.4% 100.0%36.0% 38.0% 37.0%

7 7 1450.0% 50.0% 100.0%7.0% 7.0% 7.0%

23 28 5145.1% 54.9% 100.0%23.0% 28.0% 25.5%

100 100 20050.0% 50.0% 100.0%

100.0% 100.0% 100.0%

Count% within PARITY_% within GROUPCount% within PARITY_% within GROUPCount% within PARITY_% within GROUPCount% within PARITY_% within GROUPCount% within PARITY_% within GROUP

G2

G3

G4

Primi

PARITY_

Total

FerrousSulphate Carbonyl Iron

GROUP

Total

Conclusion: P-value of 0.718(insignificant) indicates the

distribution of parity does not differ across Ferrous Sulphate Group and

Carbonyl Iron Group

63

Comparison of Gestational Age between Ferrous Sulphate Group

and Carbonyl Iron Group

Group Statistics

27.7200 2.3444828.2814 2.55750


GES_AGEMean Std. Deviation


-1.618 198 .107 -.5614 -1.24559 .12279GES_AGEt df P-value



Difference


Conclusion: P-value of 0.107 indicates the difference in

gestational age between Ferrous Sulphate Group and Carbonyl Iron

Group is insignificant.

64

Comparison of Initial Hb between Ferrous Sulphate Group and

Carbonyl Iron Group

Group Statistics

8.7790 .386208.8660 .35653


INIT_HBMean Std. Deviation


-1.655 198 .099 -.0870 -.19065 .01665INIT_HBt df P-value



Difference


Conclusion: P-value of 0.099 indicates the difference in Initial Hb

between Ferrous Sulphate Group and Carbonyl Iron Group is insignificant

65

Comparison of Final Hb between Ferrous Sulphate Group and

Carbonyl Iron Group.

Group Statistics

10.0950 .5457610.4590 .55489


FINAL_HBMean Std. Deviation


-4.677 198 .000 -.3640 -.51748 -.21052FINAL_HBt df P-value



Difference


Conclusion: P-value of less than 0.001 indicates the difference

in Final Hb between Ferrous Sulphate Group and Carbonyl Iron Group is

highly significant(significant at 1%).

.001

66

Comparison of Rise in Hb between Ferrous Sulphate Group and

Carbonyl Iron Group.

Group Statistics

1.3190 .301411.6080 .28909


RISE_HBMean Std. Deviation

Conclusion: P-value of less than 0.001 indicates the difference in

“Rise in Hb” between Ferrous Sulphate Group and Carbonyl Iron Group is

highly significant (significant at 1%).


-6.920 198 .001 -.2890 -.37136 -.20664RISE_HBt df P-value



Difference


67

DISCUSSION

Anemia is the commonest medical disorder in pregnancy.

Iron deficiency can be corrected by administration of iron. The

goal of treatment is to identify anemia at an earlier gestational

age and treatment should be aimed at increasing hemoglobin

level as rapidly as possible so as to decrease the maternal and

fetal morbidity and mortality.

Ferrous sulphate iron tablet is available in all government

hospitals and hence the result obtained with Ferrous sulphate

and corbonyl iron were compared.

In my study only moderately anemic pregnant patients were

selected due to ethical reasons that severely anemic pregnant

women needs blood transmission.

In both groups majority of the patients had microcytic

hypochromic blood picture followed by normocytic hypochromic

blood picture.

68

In my study Carbonyl Iron showed a better rise in Hb

percentage than ferrous sulphate (P value 0.001) which is

significant at 1%. This is consistent with the observation made by

Adul BB, Desai A, Gawde A, Baliga B in which there was a

significant increase in average Hb level (P

69

In my study rise in Hb was a good predictor for the

response of iron treatment in anemic pregnant women. This is

similar to the observation made by Freire WB Am J Clin Nutr

1989 Dec.

The adverse effect profile was in favor of carbonyl iron in

my study with less gastrointestinal toxicity this was similar to the

study by Gordeuk VR Brittenham GM, Mclaren CE, Hughes Ma,

Keating LJ March 1986.

With respect to cost benefit analysis the cost of ferrous

sulphate tablets accounts to Rs. 75/- for 1 month. The cost of

carbonyl iron for 1 month amounts ti Rs. 240/- for 1 month. Hence

in affordable group carbonyl iron is preferred.

70

SUMMARY

In my study 54% of Carbonyl iron group showed a rise of

1.5-2 gm % and 12% showed a rise of more than 2 gm % of

hemoglobin whereas in ferrous sulphate group 66% showed a

rise of 1-1.5 gm % and 22% showed a rise of 1.5-2gm % and

none showed a rise of more than 2 gm % hemoglobin

Rise in hemoglobin percentage was better with

carbonyl iron than ferrous sulphate.

Carbonyl iron had less toxic to gastrointestinal

mucosa.

Patients compliance was better with carbonyl iron.

It is safer than ferrous sulphate as there is less risk of

causing poisoning due to over dosage.

Carbonyl iron is inert and consists of small particles of

metallic iron.

71

CONCLUSION

This study shows that the efficacy of carbonyl iron is

significantly more than ferrous sulphate, even though the relative

cost is more.

Affordable persons can be offered carbonyl iron.

In resource poor settings effective treatment of moderate

anemia is possible with ferrous sulphate if diagnosed at an earlier

stage.

Further large scale studies will raise the curtain for a better

understanding of the effect of different iron preparation on

different types of anemia.

PROFORMA

PATIENT NAME : AGE:

ADDRESS : OBSTETRICSTATUS

LMP

EDD

DISSERTATION REF NO:

SOCIOECONOMIC STATUS

HT WT BMI GA

TYPE OF IRON DATE OF STARTINGTREATMENT

PAST H/O

H/O ANY DISEASES IN THE PAST

IF YES, SPECIFY THE DISEASE

CLINICAL EXAMINATION USG

INVESTIGATION

DAY – 0 DAY – 30Hb gm% Hb gm%Hct % Hct %Peripheral SmearMCV MCVMCHC MCHCBT / CTMotion - Ova / Cyst

SIDE EFFECTS NOTED ON 15th DAY

BIBLIOGRAPHY

1. Bioavailability of cabonyl iron: a randomized double-blind

study. Devasthali SD, Gordeuk VR, Brittenham GM,Bravo

JR, Hughes MA, Keating LJ. Eur J Haematol 1991 May

2. High-dose carbonyl iron for iron deficiency anemia :a

randomized double-blind trial. Gordeuk VR, Brittenham GM,

Hughes.M, Keatinig.L, Opplt JJ. Am J Clin Nutr. 1987

December

3. Carbonyl iron for short-term supplementation in female

anemic patients. Gordeuk VR, Brittenham GM, Hughes M,

Keatinig L 1987 January- February

4. Absorption of carbonyl iron. Huebers HA, Brittenham GM,

Csiba E, Finch CA. J Lab Clin Med.1986 November

5. Carbonyl iron therapy for iron deficiency anemia. Gordeuk

VR, Brittenham GM, McLaren CE, Hughes MA, Keating LJ.

1986 March

6. Comparative assessment of the bioavailability, efficacy and

safety of a modified-release (MR) carbonyl iron tablet and

oral conventional iron preparationin adult Indian patients

with nutritional iron deficiency anaemia. Adsul BB, DesaiA,

Gawde A, Baliga V. J Indian Med Assoc. 2005 June

7. Iron status in anemic pregnant women. Thinkhamrop J,

Apiwantanakul S, Lumbiganon P, Buppasiri P. J Obstet

Gynaecol Res. 2003 June

8. Iron-deficiency anemia: diagnosis and therapy Tichelli A,

Gratwohl A, Speck B. Schweiz Med Wochenschr. 1992

March

9. Prevention of iron dificiencywith carbonyl iron infemale

blood donors. Gordeuk VR, Brittenham GM, Bravo J,

Hughes MA, Keating LJ. Department of Medicine,

Cleveland Metropolitan General Hospital, Ohio.

Transfusion. 1990 March –April

10. Hemoglobin as a predictor of response to iron therapy and

its use in screening and prevalence estimates. Freire WB.

Am J Clin Nutr. 1989 December.

11. Supplementary iron dose in pregnancy anemia prophylaxis.

Reddaiah VP, Raj PP, Ramachandran K, Nath LM, Sood

SK, Madan N, Rusia U. Indian J Pediatr. 1989 January

12. Process of carbonyl iron absorption form the rat duodenal

mucosa. Nakamura T, Mori M, Awai M. Department of

Pathology, Okayama University Medical School, Japan.

Acta Pathol Jpn.1988 November

13. The effects of short-term oral iron therapy on developmental

deficits in iron-deficient anemic infants. Lozoff B,

Brittenham GM, Viteri FE, Wolf AW, Urrutia JJ. J Pediatr.

1982 March

14. Comparative bioavailability of elemental iron powders for

repair of iron deficiency anemia in rats. Studies of efficacy

and toxicity of carbonyl iron. Sacks PV, Houchin DN. Am J

Clin Nutr. 1978 April

15. Iron therapy and hemoglobin regeneration in pregnancy

anemias and postpartum anemias Schwab J,GH ltner E. Z

Geburtshilfe Perinatol. 1977 October

16. Iron supplementation during pregnancy, anemia, and birth

weight: a randomized controlled trial. Cogswell ME,

parvanta I, Ickes L, Yip R, Brittenham GM. Am J Clin Nutr.

2003 October

17. Iron prophylaxis in pregnancy: intravenous route versus oral

route. Bencaiova G, von Mandah U, Zimmermann R. Eur J

Obstet GynecolReprod Biol. 2009 June

18. Iron Supplementation in pregnancy-does the preparation

matter? Melamed N, Ben-Haroush A, Kaplan B, Yogeb Y.

Arch GynecolObstet. 2007 December

19. Prevention of iron deficiency anemia in adolescent and

adult pregnancies. Meier PR, Nickerson HJ, Olson KA,

Berg RL, Meyer JA. Department of Obs , Marshfield Clinic,

USA. Clin Med Res. 2003 January.

20. The effectiveness of three regimens using ferrous sulfate to

treat anemia in pregnant women de Souza AI, Batista Filho

M, Ferreira LO, Figueir Ha JN. Rev Panam Salud Publica.

2004 May

21. Intermittent iron supplementation regimens are able to

maintain safe maternal hemoglobin concentrations during

pregnancy in Venezuela. Pena-Rosas JP, Nesheim MC,

Garcia-Casal MN, Crompton DW, Division of Nutritional

Sciences, Cornell University, Ithaca, NY, USA. J Nutr. 2004

May

22. Impact of daily versus weekly hematininc supplementation

on anemia in pregnant women. Gomber S, Agarwal KN,

Mahajan C, Agarwal N. Indian Pediatr. 2002 April

23. Daily ironsupplementation is more effective than twice

weekly iron suplementationin pregnant women in Pakistan

in a randomized double-blind clinical trial. Mumtaz Z,

Shahab S, Butt N, Rab MA, Health Services Academy,

West BlueArea, Islamabad, Pakistan. J Nutr. 2000

November

24. Iron requirements in pregnancy and strategies to meet

them. Bothwell TH Department of Medicine, University

of With watersrand Medical School, Johannesburg, South

Africa. Am J Clin Nutr. 2000 July

25. Effect of dose and formulation on iron tolerance in

pregnancy. Shatrugna V, Raman L, Kailash U, Balakrishan,

N, Rao KV. National Institute of Nutrition, Indian council of

Medical Research, Andhra Pradesh, India. Natl Med J

India. 1999January-Febuary

26. Iron supplementation in pregnancy: A randomized, placebo

controlled trial of low dose iron supplementation with and

without heme iron. Eskeland B, Malterud K, Ulvik RJ,

Hunskaar S. Department of public Health and primary

Health Care, University of Bergen, Norway Acta Obstet

Gynecol Scand. 1997 October

27. Pregnancy associated anemia and iron :a pilot study. Rani

NV, Pandey J, Das B, Shruti, Talib VH, Department of

Laboratory Medicine, Safdarjang Hospital, New Delhi.

Indian J Pathol Microbiol. 1995 July

28. Women’s nutritional status, iron consumption and weight

gain during pregnancy in relation to neonatal weight and

length in West Java, Indonesia. Achadi EL, Hansell MJ,

Sloan NL, Anderson MA. Center for Child Survival,

University of Indonesia, West Java. Int Jgynaecol Obstet.

1995 June

29. A Comparative study of the effectiveness of iron

preparations in the treatment of iron deficiency anemia in

pregnant women (Article in Russian) Buglanov AA,

Saiapina EV, TuraevAT. Akush Ginekol (Mosk). 1994

30 Pathophysiological mechanisms of formation of iron

deficiency states and modern approaches to administration

of oral forms of iron preparations in their prophylaxis and

treatment Article in Ukrainian Lik Sprava. 2003 January-

Februarys

31. Results of therapy of anemia in pregnancy Article in

German Fischer H, Meller K. Medizinisch-Poliklinisches

Institut, University Leipzig. Zentralbl Gynakol.1992

32. Supplementary iron dose in pregnancy anemia prophylaxis.

FeddaiahVP, Raj PP, Ramachandran K, Nath LM, Sood

SK, Madan N, Rusia U. Indian J Pediatr. 1989 January-

February

33. Iron-storage deficiency and iron supplementation in

pregnancy. Dommisse J, Bell DJ, DU Toit ED, Midgley V,

choen M. S Afr Med J. 1983 December

34. A comparison of two combined iron-folic acid preparations

in the prevention of anemia in Pregnacy. Gringras M. J Int

Med Res. 1982

35. Treatment of anemia in pregnancy Article in German

Steiner H, Hilgarth M. Fortschr Med. 1977 March

36. Iron therapy in pregnancy; a comparative study of various

modes. DEVOE RW, MOSES LE. Calif Med. 1954

November

37. Treatment and prevention of iron deficiency anemia Article

in Russian Miterev IuG, Voronina LN. Klin Med (Mosk).

1989 August

38. Response of hemoglobin, serum ferritin, and serum

transferring receptor during iron supplementation in

pregnancy: a prospective study. Madhavan Nair K,

Bhaskaram P, Balakrishna N, Ravinder P Division of

Biophysics, National Institute of Nutrition, Indian Council of

Medical Research, Hyderabad, India.

nairthayilehotmail.com Nutrition. 2004 October

39. Prevention of iron-deficiency anemia in pregnancy using

early iron supplementation: a controlled trial Article in

French De Benaze C, Galan P, Wainer R, Hercberg S.

Centre de Recherche sur les Antmies Nutritionnelles,

CNAM, Paris. Rev Epidemiol Sante Publique. 1989

40. A prospective, Partially randomized study of pregnancy

outcomes and hematological responses to oral and

intramuscular iron treatment in moderately anemic pregnant

women. Sharma JB, Jain S, Mallika V, Singh T, Kumar A

Arora R, Murthy NS. Department of Obs Gynec, Mulana

Azad Medical College and Lok Nayak Hospital, New Delhi

41. Efficacy of iron therapy: a comparative evaluation of four

iron preparations administered to anaemic pregnant

women. Fochi F, Ciampini M, Ceccarelli G. J Int Med Res.

1985

42. Low compliance with an iron-supplementation program: a

study among pregnant women in Jakarta, Indonesia.

Schultink W, van der Ree M, Matulessi P, Goss R. South

East Asian Ministries of Education Organization-Tropical

Medicine (SEAMEO-TROPMED) Center, Jakarta,

Indonesia. Am J Clin Nutr. 1993 February

43. Studies on iron metabolism and iron deficiency anemia in

pregnant women-theoretical discussion on the relation

between serum iron level and iron dose to be administered,

and clinical result after iron therapy. Article in Japanese

Kurabayashi M. Nippon Sanka Fujinka Gakkai Zasshi. 1980

July

44. Iron requirements of pregnancy. NAACOGS Clin Issu

Perinat Womens Health Nurs. 1991

45. Iron supplementation studies among pregnant women.

Kuizon MD, Platon TP, Ancheta Lp, Angeles JC, Nunez CB,

Macapinlac MP. Southeast Asian J Trop Med Public

Health. 1979 December

46. Effect of oral iron supplementation during pregnancy on

maternal and fetal iron status. Wallenburg HC, van Eijk HG.

J Perinat Med. 1984.

47. Hemoglobin correction factors for estimating the prevalence

of iron deficiency anemia in pregnant women residing at

high altitudes in Bolivia. Cohen JH, Hass JD. Cornell

University, Division of Nutritional Sciences, Ithaca, New

York, USA Rev Panam Salud Publica. 1999 December

48. Treatments for iron-deficiency anaemia in pregnancy. RevizL, Gyte GM, Cuervo LG. Cochrane Database Syst Rev.2007 April

49. Side effects of oral iron prophylaxis in pregnancy-myth orreality? Milman N,Byg KE, Bergholt T, Eriksen L.Department of Obs Gentofte Hospital,Copenhangen,Denmark. Milmanch.dk Acta Haematol. 2006

50. Oral versus high dose parenteral iron supplementation inpregnancy. Mumar A, Jain S, Singh NP, Singh T.Department of Obs Gynec, Mulana Azad Medical Collegeand Lok Nayak Hospital, New Delhi Int J Gynaecol Obstet.2005 April

51. Intermittent oral iron supplementation during pregnancy.Goonewardene M, Liyanage C, Fernando R. Department ofObstetrics and Gynaecology, Faculty of Medicine,University of Ruhuna, Galle. Malikgceureka. 1k Ceylon MedJ. 2001 December

52. Current aspects of diagnosis and therapy of iron deficiencyanemia in pregnancy Article in German Breymann C;Anaemia Working Group. Praxis (Bern 1994). 2001 August

53. The effects of iron supplementation during pregnancy, givenby traditional birth attendants, on the prevalence of anaemiaand malaria. Menendez C, Todd J, Alonso PL, Francis N,Lulat S, Ceesay S, M’Boge B, Greenwood BM. MedicalResearch Council Laboratories, Fajara, Banjul, TheGambia. Trans R Soc Trop Med Hyg. 1994 September-October

to compare the efficacy of oral carbonyl iron...

Documents